2. Academic Validation
  3. The effect of polymer backbone chemistry on the induction of the accelerated blood clearance in polymer modified liposomes

The effect of polymer backbone chemistry on the induction of the accelerated blood clearance in polymer modified liposomes

  • J Control Release. 2015 Sep 10:213:1-9. doi: 10.1016/j.jconrel.2015.06.023.
Paul H Kierstead 1,  Hideaki Okochi 2,  Vincent J Venditto 2,  Tracy C Chuong 3,  Saul Kivimae 2,  Jean M J Fréchet 4,  Francis C Szoka 5
Affiliations

Affiliations

  • 1 Department of Chemistry, University of California Berkeley, Berkeley, CA 94720, USA; Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94143, USA.
  • 2 Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94143, USA.
  • 3 Department of Chemistry, University of California Berkeley, Berkeley, CA 94720, USA.
  • 4 Department of Chemistry, University of California Berkeley, Berkeley, CA 94720, USA; Physical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
  • 5 Department of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: szoka@cgl.ucsf.edu.
PMID: 26093095 DOI: 10.1016/j.jconrel.2015.06.023
Abstract

A variety of water-soluble Polymers, when attached to a Liposome, substantially increase Liposome circulation half-life in Animals. However, in certain conditions, liposomes modified with the most widely used polymer, polyethylene glycol (PEG), induce an IgM response resulting in an accelerated blood clearance (ABC) of the Liposome upon the second injection. Modification of liposomes with Other water-soluble polymers: HPMA (poly[N-(2-hydroxypropyl) methacrylamide]), PVP (poly(vinylpyrrolidone)), PMOX (poly(2-methyl-2-oxazoline)), PDMA (poly(N,N-dimethyl acrylamide)), and PAcM (poly(N-acryloyl morpholine)), increases circulation times of liposomes; but a precise comparison of their ability to promote long circulation or induce the ABC effect has not been reported. To obtain a more nuanced understanding of the role of polymer structure/MW to promote long circulation, we synthesized a library of polymer diacyl chain lipids with low polydispersity (1.04-1.09), similar polymer molecular weights (2.1-2.5kDa) and incorporated them into 100nm liposomes of a narrow polydispersity (0.25-1.3) composed of polymer-lipid/hydrogenated soy phosphatidylcholine/Cholesterol/diD: 5.0/54.5/40/0.5. We confirm that HPMA, PVP, PMOX, PDMA and PAcM modified Liposome have increased circulation times in rodents and that PVP, PDMA, and PAcM do not induce the ABC effect. We demonstrate for the first time, that HPMA does not cause an ABC effect whereas PMOX induces a pronounced ABC effect in rats. We find that a single dose of liposomes coated with PEG and PMOX generates an IgM response in rats towards the respective polymer. Finally, in this homologous polymer series, we observe a positive correlation (R=0.84 in rats, R=0.92 in mice) between the circulation time of polymer-modified liposomes and polymer viscosity; PEG and PMOX, the Polymers that can initiate an ABC response were the two most viscous Polymers. Our findings suggest that Polymers that do not cause an ABC effect such as, HPMA or PVP, deserve further consideration as polymer coatings to improve the circulation of liposomes and Other nanoparticles.

Keywords

Accelerated blood clearance; Anti-polymer IgM; Biodistribution; Pharmacokinetics; Polyethylene glycol; Polymer modified liposomes; RAFT polymerization.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z